Previous studies of cold insouble globulin (CIG) have directly or indirectly associated its opsonic activity with the function of the sessile macrophages of the reticuloendothelial system (RES), particularly to the Kupffer cells of liver. The research described herein examines the role of CIG in aiding macrophages to carry out those functions normally performed only by nonsessile macrophages, e.g. the cytostasis and/or cytotoxicity of peripheral malignant cells or the removal of cell debris as part of the normal wound healing process. A model system developed in this laboratory will be used to determine the characteristics of CIG interactions with both macrophages and target particles including sickled erythrocytes and tumor cells in culture. Studies using standard assays for cytostasis and cytotoxicity of cultured neoplastic cell lines, with/without added macrophages and CIG, will be performed to determine if CIG acts directly, or in conjunction with macrophages to express these functions. The in vivo effect of elevated or depressed levels of CIG on metastasis rate will also be determined using a mouse salivary gland carcinoma model system. Using appropriate counting and microscopic techniques with 125I, fluorescein or ferritin labeled CIG, the binding of CIG to cellular debris in vivo and in vitro will be studied. The interaction of macrophages with the CIG-cell debris complex in clearing the wound will also be characterized. Both experimentally produced injuries and the "natural", chronic ulcers of patients with sickle cell anemia will be studied. The therapeutic use of CIG in the treatment of these chronic ulcers and patients with extensive burns will also be determined. Further studies will examine the sequestration of CIG at the site of an injury in patients who have undergone radical mastectomy.